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Effect of hospital volume on postoperative mortality and survival after oesophageal and gastric cancer surgery in the Netherlands between 1989 and 2009
European Journal of Cancer (2012) 48, 1004– 1013
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Effect of hospital volume on postoperative mortality and survival after oesophageal and gastric cancer surgery in the Netherlands between 1989 and 2009 Johan L. Dikken a,b, Anneriet E. Dassen c, Valery E.P. Lemmens d, Hein Putter e, Pieta Krijnen f, Lydia van der Geest f, Koop Bosscha c, Marcel Verheij b, Cornelis J.H. van de Velde a,⇑, Michel W.J.M. Wouters a,g a
Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, The Netherlands Department of Radiotherapy, The Netherlands Cancer Institute – Antoni Leeuwenhoek Hospital, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands c Department of Surgery, Jeroen Bosch Ziekenhuis, Henri Dunantstraat 1, 5223 GZ Den Bosch, The Netherlands d Comprehensive Cancer Center South, Zernikestraat 29, 5612 HZ Eindhoven, The Netherlands e Department of Medical Statistics, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, The Netherlands f Comprehensive Cancer Center The Netherlands, Schuttersveld 2, 2316 ZA, Leiden, The Netherlands g Department of Surgery, The Netherlands Cancer Institute – Antoni Leeuwenhoek Hospital, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands b
KEYWORDS Oesophageal neoplasms Stomach neoplasms Gastrectomy Oesophagectomy Quality indicators – health care Quality assurance – health care Quality of health care Hospital mortality Survival
Abstract Background: High hospital volume is associated with better outcomes after oesophagectomy and gastrectomy. In the Netherlands, a minimal volume standard of 10 oesophagectomies per year was introduced in 2006. For gastrectomy, no minimal volume standard was set. Aims of this study were to describe changes in hospital volumes, mortality and survival and to explore if high hospital volume is associated with better outcomes after oesophagectomy and gastrectomy in the Netherlands. Methods: From 1989 to 2009, 24,246 patients underwent oesophagectomy (N = 10,025) or gastrectomy (N = 14,221) in the Netherlands. Annual hospital volumes were defined as very low (1–5), low (6–10), medium (11–20), and high (P21). Volume–outcome analyses were performed using Cox regression, adjusting for year of diagnosis, case-mix and the use of multimodality treatment. Results: From 1989 to 2009, the percentage of patients treated in high-volume hospitals increased for oesophagectomy (from 7% to 64%), but decreased for gastrectomy (from 8% to 5%). Six-month mortality (from 15% to 7%) and 3-year survival (from 41% to 52%) improved after oesophagectomy, and to a lesser extent after gastrectomy (6-month mortality:
⇑ Corresponding author: Address: Leiden University Medical Center, Department of Surgery, K6-R, P.O. Box 9600, 2300 RC Leiden, The Netherlands. Tel.: +31 71 526 2309; fax: +31 71 526 6750. E-mail address: [email protected] (C.J.H. van de Velde).
0959-8049/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ejca.2012.02.064
J.L. Dikken et al. / European Journal of Cancer 48 (2012) 1004–1013
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15%-10%, three-year survival: 55–58%). High hospital volume was associated with lower 6month mortality (hazard ratio (HR) 0.48, P < 0.001) and longer 3-year survival (HR 0.77, P < 0.001) after oesophagectomy, but not after gastrectomy. Conclusions: Oesophagectomy was effectively centralised in the Netherlands, improving mortality and survival. Gastrectomies were mainly performed in low volumes, and outcomes after gastrectomy improved to a lesser extent, indicating an urgent need for improvement in quality of surgery and perioperative care for gastric cancer in the Netherlands. Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction Oesophageal and gastric cancers are highly lethal malignancies.1 Despite surgery, which is the cornerstone of curative treatment for these diseases, survival is low, and compared to other surgical procedures, postoperative mortality is high. In the Western world, 5-year survival rates are below 25% for oesophageal cancer,2,3 and do not exceed 40% for gastric cancer.2,4 Reported postoperative mortality after oesophagectomy varies from 2% for specialised centres5 to 10% for certain nationwide registries.6 After gastrectomy, postoperative mortality varies between 3% to well above 10%.7,8 To reduce mortality and improve survival, it has been suggested that these high-risk operations should be performed in specialised centres with adequate annual volumes. Many studies have investigated volume–outcome relations after oesophagectomy and gastrectomy, but the relative importance of volume after gastrectomy in particular is disputed.9,10 In the Netherlands, a relation between high hospital volume and low postoperative mortality was demonstrated for oesophagectomy in 2000.11 Despite extensive discussions within the Dutch Society of Surgery, this study did not lead to significant changes in referral patterns for oesophagectomies on a national level. Therefore, as of 2006 a minimum volume of 10 oesophagectomies per year was enforced by the Dutch Healthcare Inspectorate, and as of 2011 the Dutch Society of Surgery recommends a minimal volume of 20 oesophagectomies per year. For gastrectomy, no minimum volume standard has been established in the Netherlands. Aims of the present study were to describe changes in annual hospital volumes, postoperative mortality, survival and lymph node yields for oesophagectomy and gastrectomy in the Netherlands between 1989 and 2009, and to explore whether there is any association between annual hospital volume for oesophagectomy and gastrectomy and postoperative mortality, survival and lymph node yield.
Netherlands, a country of 16.5 million inhabitants. Information on all newly diagnosed malignancies is routinely collected by trained registrars from the hospital records 6–18 months after diagnosis. Quality and completeness of the data are high.12 Topography and morphology were coded according to the International Classification of Diseases for Oncology (ICD-O).13 ICD-O morphology codes were used to classify tumours as adenocarcinoma (8140-8145, 8190, 8201-8211, 8243, 8255-8401, 8453-8520, 8572, 8573, 8576), squamous cell carcinoma (SCC) (8032, 8033, 8051-8074, 8076-8123) and other or unknown histology (8000-8022, 8041-8046, 8075, 8147, 8153, 8200, 82308242, 8244-8249, 8430, 8530, 8560, 8570, 8574, 8575). Tumours were staged according to the International Union Against Cancer (UICC) Tumour Node Metastases (TNM) classification in use in the year of diagnosis. Vital status was initially obtained from municipal registries, and from 1994 onwards from the nationwide population registries network. These registries provide complete coverage of all deceased Dutch citizens. Follow-up was complete for all patients until 31st December 2009. The study was approved by the NCR Review Board. 2.2. Patients Between January 1989 and December 2009, 71,090 patients with oesophageal or gastric cancer were diagnosed in the Netherlands (Fig. 1). Patients who did not undergo surgical treatment (N = 43,646) and patients without information on the hospital where the diagnosis was established, or where surgery was performed (N = 8), were excluded, leaving 27,436 resections available to calculate annual hospital volumes. After establishing annual hospital volumes, patients with insitu carcinoma (N = 288), and patients with distant metastases (N = 2902) were excluded, leaving 24,246 patients with non-metastatic invasive carcinoma available for volume–outcome analyses. 2.3. Surgery
2. Patients and methods 2.1. The Netherlands Cancer Registry Data were obtained from the Netherlands Cancer Registry (NCR), which covers all hospitals in the
Since the NCR is a topography-based registry, and the type of surgery was not specified for every patient, the distinction between oesophageal and gastric cancer surgery was based on tumour location. Oesophagectomies were defined as resections for cancers of the
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J.L. Dikken et al. / European Journal of Cancer 48 (2012) 1004–1013 Netherlands Cancer Registry 1989-2009 Diagnosis of oesophageal orgastric cancer N = 71,090 Excluded (N = 43,646) No resection Excluded (N = 8) No hospital in registry Resection for oesophageal or gastric cancer N = 27,436
Calculation of Annual Hospital Volumes
Excluded (N = 3,190) In-situ/metastatic disease Resection for M0 oesophageal or gastric cancer N = 24,246
Mortality and Survival Analyses
Fig. 1. Study profile.
oesophagus (C15.0-15.9) and gastric cardia (C16.0), whereas gastrectomies were defined as resections for non-cardia gastric cancer (C16.1-16.9). To ensure this distinction did not influence the results, volume–outcome analyses were repeated with cardia cancer coded as gastric cancer. Yearly resection rates were calculated as the number of resections relative to the number of cancers diagnosed in a year. 2.4. Hospital volumes Annual hospital volumes were defined as the number of oesophagectomies or gastrectomies per hospital per year. Clinically relevant volume categories were defined as very low (1–5/year), low (6–10/year), medium (11–20/ year), and high (P21/year). From 2005 to 2009, the hospital where the surgery was performed was registered for all patients. Before 2005, the hospital where the surgery was performed was only registered in 53% of the cases, and showed an 80% overlap with the hospital of diagnosis. For the remaining 47%, with an unknown surgical hospital, the hospital of diagnosis was used to calculate hospital volume. 2.5. Statistical analysis Oesophagectomy and gastrectomy were analysed separately. Resection rates and hospital volumes over time were analysed with the Chi-square test. Changes in 6month mortality and 3-year survival were analysed with stratified Cox regression, adjusted for sex, age, socioeconomic status,14 stage, morphology, preoperative therapy use and postoperative therapy use (only for 3year survival). Overall survival (OS) was calculated from the day of diagnosis until death, because the date of surgery was not available before 2005. Six-month OS was calculated unconditionally, while 3-year OS was calculated conditionally on surviving the first 6 months after
diagnosis. Lymph node yields over time were adjusted for sex, age, stage and morphology. For volume–outcome analyses, the patient was considered the unit of analysis, with hospital volume as the exposure factor. Differences in survival estimates were calculated with Cox regression, stratified for hospital volume and adjusted for the factors used to analyse changes over time and for clustering of deaths within hospitals.15 Differences in lymph node yields were analysed with generalised estimated equations, adjusted for the factors used to analyse changes over time and for clustering within hospitals. Besides analysing hospital volume in categories, annual volume was analysed as a linear variable. Analyses were performed with SPSS (version 17.0.2) and R (version 2.12.2). 3. Results 3.1. Patient characteristics Between 1989 and 2009, 24,246 patients with resectable, non-metastatic oesophageal (N = 10,025) or gastric cancer (N = 14,221) underwent a resection in the Netherlands. Patient characteristics (Tables 1 and 2) varied between the different volume categories. For oesophageal cancer, high-volume hospitals treated more patients with squamous cell carcinoma and more advanced tumour stages. For gastric cancer, patients treated in high-volume hospitals were older and had more advanced tumours. 3.2. Hospital volumes over time From 1989 to 2009, the annual number of oesophagectomies doubled (from 352 to 723), and the annual number of gastrectomies steadily decreased (from 1107 to 495) (Fig. 2).
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Table 1 Patient characteristics for all surgically treated patients with non-metastatic invasive oesophageal cancer in the Netherlands between 1989 and 2009 (N = 10,025). VLV (1–5)
Total Sex Male Female Age category <60 60–75 >75 SES Low Medium High Unknown Morphology Adenocarcinoma SCC Other TNM stage I II III IVa Unknown Preoperative therapy Yes No Postoperative therapy Yes No
LV (6–10)
MV (11–20)
HV (P21)
P
N
%
N
%
N
%
N
%
2914
100
2695
100
1494
100
2922
100
2213 701
76 24
2058 637
76 24
1130 364
76 24
2249 673
77 23
0.73
936 1630 348
32 56 12
956 1456 283
35 54 11
515 814 165
34 54 11
1032 1632 258
35 56 9
0.002
274 2415 135 90
9 83 5 3
308 2124 123 140
11 79 5 5
165 1208 53 68
11 81 4 5
259 2131 115 417
9 73 4 14
<0.001
2288 554 72
79 19 2
2006 628 61
74 23 2
1113 341 40
74 23 3
2134 732 56
73 25 2
<0.001
622 1161 988 30 113
21 40 34 1 4
512 1093 940 30 120
19 41 35 1 4
285 576 535 23 75
19 39 36 2 5
522 1068 1112 25 195
18 37 38 1 7
<0.001
165 2749
6 94
244 2451
9 91
357 1137
24 76
938 1984
32 68
<0.001
144 2770
5 95
145 2550
5 95
91 1403
6 94
151 2771
5 95
0.43
VLV: Very Low Volume (1–5 resections/year) LV: Low Volume (6–10 resections/year), MV: Medium Volume (11–20 resections/year), HV: High Volume (P21 resections/year), SES: Socio Economic Status, SCC: squamous cell carcinoma, preoperative/postoperative therapy: chemotherapy with/without radiotherapy. a T4N1-3M0 and T1-4N3M0 gastric cancers were assigned stage IV in the 6th edition TNM-classification
The percentage of oesophagectomies performed in high-volume hospitals increased from 7% to 64%, while the number of gastrectomies performed in high-volume hospitals decreased from 8% to 5%. In 2009, 44 of the 92 hospitals (48%) in the Netherlands performed oesophagectomies, and 91 of the 92 hospitals performed gastrectomies. 3.3. Resection rates, mortality, survival and lymph node yields over the years Resection rates slightly decreased for oesophageal cancer (from 1989 to 2009: 31–29%, P < 0.01), and strongly decreased for gastric cancer (56–37%, P < 0.01). Adjusted 6-month mortality after oesophagectomy decreased from 14.8% in 1989 to 7.1% in 2009 (P < 0.001), while adjusted 6-month mortality after gastrectomy decreased to a lesser extent: from 15.2% in 1989 to 9.9% in 2009 (P < 0.001) (Fig. 3a). Adjusted 3year conditional survival significantly increased after oesophagectomy: from 41.0% in 1989 to 52.2% in 2009 (P < 0.001). Adjusted 3-year conditional survival after
gastrectomy increased to a lesser extent: from 55.0% in 1989 to 58.4% in 2009 (P < 0.01) (Fig. 3b). The improvement in 6-month mortality and 3-year survival over time was significantly stronger after oesophagectomy, when compared to gastrectomy (both P < 0.01). Mean lymph node yield after oesophagectomy increased from 10.1 in 1999 to 16.2 in 2009 (P < 0.001), and mean lymph node yield after gastrectomy increased from 8.1 in 1999 to 12.4 in 2009 (P < 0.001). 3.4. Volume–outcome relations Results from the multivariable analyses on volume– outcome relations are shown in Table 3. After oesophagectomy, medium and high volume hospitals were associated with lower six-month mortality and longer three-year conditional survival when compared to very-low volume hospitals (Fig. 4). After gastrectomy, neither six-month mortality or three-year conditional survival were associated with hospital volume category (Fig. 5). High hospital volume was associated with high
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Table 2 Patient characteristics for all surgically treated patients with non-metastatic invasive gastric cancer in the Netherlands between 1989 and 2009 (N = 14,221). VLV (1-5)
Total Sex Male Female Age category <60 60–75 >75 SES Low Medium High Unknown Morphology Adenocarcinoma Other TNM stage I II III IVa Unknown Preoperative therapy Yes No Postoperative therapy Yes No
LV (6-10)
MV (11-20)
HV (P21)
P
N
%
N
%
N
%
N
%
3411
100
6099
100
4356
100
355
100
1987 1424
58 42
3707 2392
61 39
2646 1710
61 39
224 131
63 37
0.045
689 1606 1116
20 47 33
1270 2917 1912
21 48 31
837 2074 1445
19 48 33
53 165 137
15 46 39
0.016
378 2665 118 250
11 78 3 7
783 4846 230 240
13 79 4 4
560 3559 106 131
13 82 2 3
53 294 8 0
15 83 2 0
<0.001
3336 75
98 2
5985 114
98 2
4287 69
98 2
352 3
99 1
0.11
1299 898 936 181 97
38 26 27 5 3
2279 1675 1718 248 179
37 27 28 4 3
1687 1187 1204 154 124
39 27 28 4 3
147 78 111 11 8
41 22 31 3 2
0.014
167 3244
5 95
303 5796
5 95
138 4218
3 97
8 347
2 98
<0.001
139 3272
4 96
236 5863
4 96
122 4234
3 97
12 343
3 97
0.009
VLV: Very Low Volume (1–5 resections/year) LV: Low Volume (6–10 resections/year), MV: Medium Volume (11–20 resections/year), HV: High Volume (P21 resections/year), SES: Socio Economic Status, preoperative/postoperative therapy: chemotherapy with/without radiotherapy. a T4N1-3M0 and T1-4N3M0 gastric cancers were assigned stage IV in the 6th edition TNM-classification
lymph node yield both after oesophagectomy and gastrectomy. When analysing hospital volume as a linear covariate, volume–survival results remained the same. No changes in the results were found when volume–outcome relations were analysed with surgery for cardia cancer coded as gastrectomy (data not shown). 4. Discussion Over the study period, the number of oesophagectomies performed in high volume hospitals considerably increased, while in 2009 most gastrectomies were performed in low volume hospitals. Both 6-month mortality and 3-year survival improved after oesophagectomy, but to a lesser extent after gastrectomy. In the current dataset, a volume–survival relation was revealed for oesophagectomy, but not for gastrectomy. Since Luft et al. published the first study on volume– outcome relations for surgery,16 many studies have emerged investigating the effect of hospital and surgeons volume on short term and long term outcomes for a
variety of diseases, including resections for oesophageal and gastric cancers. Several large studies have shown an association between high hospital volume and low postoperative mortality both for oesophagectomy, 17–20 and gastrectomy17,20–22, but other studies did not find an association.23–25 In a meta-analysis exploring volume– outcome relations, high volume surgery was associated with lower postoperative mortality after both oesophagectomy and gastrectomy.9 A limited number of studies investigate the relation between hospital volume and long-term survival after oesophagectomy and gastrectomy, with conflicting results.7,24,26,27 Over the past two decades, the number of oesophagectomies in the Netherlands has increased, corresponding with an increasing incidence of oesophageal cancer.42 The decreasing incidence of gastric cancer explains the low number of gastrectomies currently performed in the Netherlands.28 Furthermore, the resection rate for gastric cancer dropped significantly, most likely the result of improved preoperative staging. Combined with the almost complete disappearance of surgery for reflux disease and ulcers, surgeons are decreasingly exposed to gastrectomies. This might partly be compensated by
J.L. Dikken et al. / European Journal of Cancer 48 (2012) 1004–1013
800
a 20 ≥21 11-20 6-10 1-5
6-Month Mortality (%)
Number of Resections
a
600
400
200
0 1989
1993
1997
2001
2005
10
5
0
2009
1989
1993
1997
2001
2005
2009
Year of Diagnosis
1,200
≥21 11-20 6-10 1-5
1,000
b 60 50
3-Year Survival (%)
Number of Resections
Oesophagectomy Gastrectomy
15
Year of Diagnosis
b
1009
800 600 400
Oesophagectomy Gastrectomy
40 30 20
200 10 0 1989
1993
1997
2001
2005
2009
0
Year of Diagnosis
1989
1993
1997
2001
2005
Year of Diagnosis
increasing volumes of bariatric surgery for obesity, but the surgical techniques used differ significantly. In the current study, increasing hospital volume was associated with lower mortality and increased long-term survival after oesophagectomy, but not after gastrectomy. This observation for gastrectomies might be explained by the low number of high-volume gastrectomies (2.5% of all gastrectomies in the current dataset), and the low threshold for what was considered high-volume surgery. In other studies that did find an association between gastrectomy in high volumes and good outcomes, the lower limit of high volume surgery varied from 20/year up to 264/year.17,27 The current study covers an extensive period of two decades of oesophago-gastric cancer surgery in the Netherlands, and analyses a significant population of about 25,000 patients. Unlike many of the large volume–outcome studies, the current study uses a clinical database with highly reliable data, providing complete coverage of all diagnosed cancers in the Netherlands. Furthermore, outcomes are case-mix adjusted, increasing reliability of the results.29 The absence of comorbidity in the current dataset was partly compensated by the use of SES, which can be considered a proxy for comorbidity.30 A potential bias when analysing outcomes over a long period is that preoperative staging and (perioperative)
c Mean Lymph Node Yield
Fig. 2. (a) Number of oesophagectomies per hospital volume category. (b) Number of gastrectomies per hospital volume category.
20
15
10
5 Oesophagectomy Gastrectomy
0 1999
2001
2003
2005
2007
2009
Year of Diagnosis
Fig. 3. (a) Six-month mortality for oesophagectomy and gastrectomy, adjusted for sex, age, socio-economic status, stage, morphology and use of preoperative therapy (1989–2009). Oesophagectomy, hazard ratio (HR) 0.96 for each year, P < 0.001. Gastrectomy, HR 0.98 for each year, P < 0.001. Difference between oesophagectomy and gastrectomy: P = 0.003. (b) Three-year survival rate conditional on surviving the first 6 months for oesophagectomy and gastrectomy, adjusted for sex, age, socio-economic status, stage, morphology and use of preoperative and postoperative therapy (1989–2006). Oesophagectomy, HR 0.97 for each year, P < 0.001. Gastrectomy, HR 0.99 for each year, P < 0.001. Difference between oesophagectomy and gastrectomy: P < 0.001. (c) Median lymph node yield for oesophagectomy and gastrectomy, adjusted for sex, age, stage and morphology (1999–2009). Oesophagectomy: P < 0.001. Gastrectomy: P < 0.001.
care generally improve over time. For example, endoscopic ultrasound, multislice high resolution
1010
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Table 3 Volume–outcome relations for oesophagectomy and gastrectomy (1989–2009). Mortality and survival were calculated with multivariable Cox regression, nodal yield was calculated with generalised estimated equations. Oesophagectomy
Gastrectomy a
Hospital volume Very low (1–5/yr) Low (6–10/yr) Medium (11–20/yr) High (P21/yr) Year of diagnosis 1989–1993 1994–1997 1998–2001 2002–2005 2006–2009 Sex Male Female Age category <60 60–75 >75 SES Low Medium High Unknown TNM stage I II III IV Unknown Morphology Adenocarcinoma SCC Other Preoperative therapy No Yes Postoperative therapy No Yes
b
Six-month mortality Three-year survival
LN yield
Six-month mortality Three-year survivala LN yieldb
HR
95% CI
HR
95% CI
OR 95% CI
HR
1.00 0.90 0.78 0.48
0.78–1.03 0.62–0.97 0.38–0.61
1.00 1.01 0.90 0.77
0.94–1.10 0.81–0.99 0.70–0.85
1.00 0.91 0.82 0.69 0.67
0.78–1.07 0.68–0.98 0.55–0.86 0.52–0.85
1.00 0.92 0.88 0.69 0.75
1.00 0.75
0.66–0.86
1.00 1.83 3.10
95% CI
HR
95% CI
OR 95% CI
1.00 1.00 1.00 0.91–1.09 0.95 1.10 1.00–1.22 0. 95 1.50 1.25–1.80 1. 10
0.84–1.07 0.83–1.08 0.82–1.49
1.00 0.99 0.99 0.98
0.91–1.07 0.90–1.08 0.86–1.12
1.00 1.02 0.96–1.08 0.99 0.90–1.10 1.93 1.81–2.04
0.83–1.01 0.79–0.97 0.63–0.75 0.63–0.75
1.00 0.96 1.00 0.89 1.18 1.10–1.25 0.74 1.42 1.27–1.60 0.70
0.86–1.07 0.79–1.01 0.65–0.85 0.60–0.81
1.00 0.98 0.94 0.88 0.78
0.90–1.05 0.87–1.02 0.81–0.96 0.72–0.86
1.00 1.08 1.02–1.16 1.42 1.32–1.52
1.00 0.83
0.78–0.89
1.00 1.00 1.04 1.00–1.08 0.79
0.73–0.85
1.00 0.91
0.85–0.97
1.10 1.05–1.14
1.56–2.14 2.54–3.79
1.00 1.14 1.41
1.07–1.21 1.25–1.59
1.00 1.00 0.97 0.94–1.00 2.03 0.87 0.82–0.92 3.94
1.78–2.30 3.47–4.49
1.00 1.27 1.57
1.18–1.37 1.44–1.71
1.00 0.88 0.82–0.93 0.75 0.69–0.81
1.00 0.76 0.54 0.53
0.64–0.90 0.38–0.78 0.38–0.74
1.00 1.05 1.00 1.04
0.96–1.16 0.85–1.17 0.86–1.26
1.00 0.92 0.70 0.94
0.81–1.04 0.55–0.91 0.73–1.21
1.00 1.01 1.00 1.03
0.92–1.12 0.84–1.20 0.85–1.24
1.00 1.28 1.73 3.85 1.92
1.08–1.52 1.41–2.13 2.55–5.81 1.41–2.62
1.00 2.74 5.20 9.76 2.37
2.46–3.04 4.46–6.05 7.43–12.81 2.00–2.81
1.00 1.15 1.39 1.93 1.04
1.00 1.46 2.15 3.50 1.91
1.31–1.63 1.93–2.38 3.00–4.08 1.40–2.60
1.00 2.99 5.37 8.45 2.36
2.78–3.22 5.01–5.75 7.43–9.61 1.96–2.84
1.00 1.26 1.28
1.11–1.43 0.94–1.75
1.00 1.09 1.05
0.98–1.21 0.84–1.33
1.00 1.00 1.05 0.99–1.11 1.00 0.88–1.12 1.18
0.86–1.64
0.58
0.44–0.78
1.00 0.32
0.23–0.43
1.00 0.84
0.76–0.93
1.00 0.27
0.17–0.43
1.00 1.05
0.84–1.31
1.00 1.07
0.94–1.21
1.00 1.01
0.85–1.21
1.00
1.09–1.21 1.31–1.47 1.70–2.20 0.92–1.17
1.00 1.23 1.55 2.23 1.01
1.16–1.31 1.46–1.66 2.05–2.42 0.82–1.24
1.00 0.94 0.71–1.25
HR: hazard ratio, OR: odds ratio, SES: Socio Economic Status, SCC: squamous cell carcinoma, CI: confidence interval, Bold: significant (P < 0.05). a Conditional on surviving the first six months. b 1999–2009.
computed tomography and PET computed tomography were introduced resulting in improvement of staging. Hospital volumes for oesophagectomy significantly change during the study period, with most high-volume resections performed in the more recent years. Therefore, high volume resections are intrinsically associated with better outcomes. However, adjusting for year of diagnosis offsets this effect. Another potential weakness is the unavailability of the surgery hospital for part of the patients treated before 2005. Instead, the hospital of diagnosis was used. However, this only happened in the first years of the study, when hospitals less frequently referred patients to another hospital for surgery.
A point of discussion might be that volumes are analysed on hospital level, rather than surgeon level.27,31,32 Quality of care, however, consists of more than an individual surgeon’s performance. Perioperative care, anaesthesia, ICU staffing, experience of the nursery staff and collaboration between different disciplines all contribute to outcomes associated with the performed procedure.33 The role of the surgeon is only one, yet important, factor contributing to outcome. Initiatives to improve medical and especially surgical care are legion. Randomised trials improve care by selecting appropriate treatments for certain indications,3,34 and by educating surgeons participating in
J.L. Dikken et al. / European Journal of Cancer 48 (2012) 1004–1013
a
20
High Volume* Medium Volume* Low Volume Very Low Volume
(≥21/yr) (11−20/yr) (6−10/yr) (0−5/yr)
a
* P < 0.05
High Volume Medium Volume Low Volume Very Low Volume
(≥21/yr) (11−20/yr) (6−10/yr) (0−5/yr)
15
Mortality (%)
15
Mortality (%)
20
10
10
5
5
0
0 0
1
2
3
4
5
0
6
1
2
* P < 0.05
b Overall survival (%)
Overall survival (%)
100
80
60
40
High Volume* Medium Volume* Low Volume Very Low Volume
20
(≥21/yr) (11−20/yr) (6−10/yr) (0−5/yr)
0 0
6
12
18
24
30
36
Time (Months)
3
4
5
6
Time (Months)
Time (Months)
b
1011
100
80
60
40 High Volume Medium Volume Low Volume Very Low Volume
20
(≥21/yr) (11−20/yr) (6−10/yr) (0−5/yr)
0 0
6
12
18
24
30
36
Time (Months)
Fig. 4. Volume–outcome relations for oesophagectomy. (a) Relation between volume and 6-month survival, adjusted for year of diagnosis, sex, age, socio-economic status, stage, morphology and preoperative therapy use. *P < 0.05 compared to Very Low Volume. (b) Relation between volume and 3-year survival, conditional on surviving the first 6 months, adjusted for year of diagnosis, sex, age, socio-economic status, stage, morphology and preoperative and postoperative therapy use. *P < 0.05 compared to Very Low Volume.
Fig. 5. Volume–outcome relations for gastrectomy. (a) Relation between volume and 6-month survival, adjusted for year of diagnosis, sex, age, socio-economic status, stage, morphology and preoperative therapy use. *P < 0.05 compared to Very Low Volume. (b) Relation between volume and 3-year survival, conditional on surviving the first 6 months, adjusted for year of diagnosis, sex, age, socio-economic status, stage, morphology and preoperative and postoperative therapy use. *P < 0.05 compared to Very Low Volume.
the trial.35,36 However, the majority of cancer patients are treated outside trials, and especially improvements in the process and structure of care on a nation-wide level will bring benefit to this group of patients. Many studies have advocated the centralisation of low-volume, high-risk operations, thereby improving nationwide quality of care.11,27 Centralisation of oesophageal and gastric cancer is currently performed in several European countries, whereas referral to high-volume centres is also advocated in the United States by the Leapfrog group.37 In Denmark, centralisation of gastric cancer surgery from 37 to 5 hospitals leaded to a drop in postoperative mortality from 8.4% to 2.1% over a period of 5 years.38 Unlike the Netherlands, which is a relatively small country with good infrastructure, centralisation of care in countries with large rural areas might lead to unreasonable travel burdens and problems with continuity of care after surgery. Therefore, others have advocated implementing processes that are related to excellent outcomes in low volume hospitals, but identification of these processes remains challenging.39
Meanwhile, using hospital volume as the sole basis for referral to improve outcomes is criticised.17 Although hospital volume can reliably identify groups of hospitals with better results on average, individual low volume hospitals can have excellent outcomes and vice versa. In contrast to volume-based referral, outcome based-referral avoids this problem, and has proven its value for oesophagectomy in the Western part of the Netherlands. In this area, a prospective audit was conducted to identify hospitals with excellent performance in oesophagectomy. During the five-year audit, a gradual concentration towards centres with excellent performance occurred, leading to a drop in postoperative mortality (12–4%) and an improvement in survival.40 Combining centralisation with auditing substantially adds to improvement of care.41 With auditing, providers of care are monitored and their performance is benchmarked against their peers. Auditing is performed on a national level for oesophagogastric cancer in Denmark,38 Sweden and the United Kingdom. A nationwide audit for both oesophageal and gastric cancer surgeries has started in the Netherlands as of 2011 aiming for
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complete coverage of all oesophagectomies and gastrectomies. In conclusion, enforcing centralisation for oesophagectomy in the Netherlands has resulted in a shift in annual hospital volumes: most resections are currently performed in high volume centres. For gastrectomy, no minimum number of resections was required, and the majority of gastric cancer resections were performed in low volume hospitals. However, as of 2012 gastrectomies in the Netherlands will be centralised to a minimum of 10/year, and as of 2013 to a minimum of 20/year. Oesophagectomy in high volume hospitals is associated with improved outcomes. No such relation for gastric cancer could be established in the current dataset, but only a minority of patients was treated in high volume hospitals. Over the past two decades, short-term mortality and longterm survival after oesophagectomy decreased significantly, while outcomes after gastrectomy improved to a lesser extent, indicating an urgent need for improvement in quality of surgery and perioperative care for gastric cancer in the Netherlands. Role of funding source This study was funded by the Signalling Committee on Cancer of the Dutch Cancer Society (KWF Kankerbestrijding). This funding source had no role in study design, collection, analysis, interpretation, writing of the manuscript or in the decision to submit the manuscript for publication. Conflict of interest statement None declared. References 1. Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127:2893–917. 2. SEER Cancer Statistics Review, 1975–2007. National Cancer Institute. Bethesda, MD, 2011. Available from: http://seer.cancer.gov/csr/1975_2007/. 3. Hulscher JB, Tijssen JG, Obertop H, van Lanschot JJ. Transthoracic versus transhiatal resection for carcinoma of the esophagus: a meta-analysis. Ann Thorac Surg 2001;72:306–13. 4. Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 2006;355:11–20. 5. Siewert JR, Stein HJ, Feith M, et al. Histologic tumor type is an independent prognostic parameter in esophageal cancer: lessons from more than 1000 consecutive resections at a single center in the Western world. Ann Surg 2001;234:360–7 [discussion 8–9]. 6. Bailey SH, Bull DA, Harpole DH, et al. Outcomes after esophagectomy: a ten-year prospective cohort. Ann Thorac Surg 2003;75:217–22 [discussion 22]. 7. Hannan E. The influence of hospital and surgeon volume on inhospital mortality for colectomy, gastrectomy, and lung lobectomy in patients with cancer. Surgery 2002;131:6–15.
8. Lepage C, Sant M, Verdecchia A, et al. Operative mortality after gastric cancer resection and long-term survival differences across Europe. Br J Surg 2010;97:235–9. 9. Gruen RL, Pitt V, Green S, et al. The effect of provider case volume on cancer mortality: systematic review and meta-analysis. CA Cancer J Clin 2009;59:192–211. 10. Metzger R, Bollschweiler E, Vallbohmer D, et al. High volume centers for esophagectomy: what is the number needed to achieve low postoperative mortality? Dis Esophagus 2004;17:310–4. 11. van Lanschot JJ, Hulscher JB, Buskens CJ, et al. Hospital volume and hospital mortality for esophagectomy. Cancer 2001;91:1574–8. 12. Schouten LJ, Jager JJ, van den Brandt PA. Quality of cancer registry data: a comparison of data provided by clinicians with those of registration personnel. Br J Cancer 1993;68:974–7. 13. WHO. International Classification of Diseases for Oncology (ICD-O-3). third ed., 2000. 14. Tesser P, Van Praag C, Van Dugteren F, Herweijer L, Van der Wouden H. Rapportage minderheden 1995: Rijswijk/Den Haag: Sociaal en Cultureel Planbureau/VUGA; 1995. 15. Liang KY, Zeger SL. Longitudinal data analysis using generalized linear models. Biometrika 1986;73:13–22. 16. Luft HS, Bunker JP, Enthoven AC. Should operations be regionalized? The empirical relation between surgical volume and mortality. N Engl J Med 1979;301:1364–9. 17. Birkmeyer JD, Siewers AE, Finlayson EV, et al. Hospital volume and surgical mortality in the United States. N Engl J Med 2002;346:1128–37. 18. Dimick JB, Wainess RM, Upchurch Jr GR, Iannettoni MD, Orringer MB. National trends in outcomes for esophageal resection. Ann Thorac Surg 2005;79:212–6 [discussion 7–8]. 19. Lin H-C, Xirasagar S, Lee H-C, Chai C-Y. Hospital volume and inpatient mortality after cancer-related gastrointestinal resections: the experience of an Asian country. Ann Surg Oncol 2006;13:1182–8. 20. Learn PA, Bach PB. A decade of mortality reductions in major oncologic surgery: the impact of centralization and quality improvement. Med Care 2010;48:1041–9. 21. Luft HS, Hunt SS, Maerki SC. The volume–outcome relationship: practice-makes-perfect or selective-referral patterns? Health Serv Res 1987;22:157–82. 22. Smith JK, McPhee JT, Hill JS, et al. National outcomes after gastric resection for neoplasm. Arch Surg 2007;142:387–93. 23. Ho V, Heslin MJ, Yun H, Howard L. Trends in hospital and surgeon volume and operative mortality for cancer surgery. Ann Surg Oncol 2006;13:851–8. 24. Thompson AM, Rapson T, Gilbert FJ, Park KGM. Hospital volume does not influence long-term survival of patients undergoing surgery for oesophageal or gastric cancer. Br J Surg 2007;94:578–84. 25. Finlayson EV, Goodney PP, Birkmeyer JD. Hospital volume and operative mortality in cancer surgery: a national study. Arch Surg 2003;138:721–5 [discussion 6]. 26. Birkmeyer JD, Sun Y, Wong SL, Stukel TA. Hospital volume and late survival after cancer surgery. Ann Surg 2007;245:777–83. 27. Bachmann MO, Alderson D, Edwards D, et al. Cohort study in South and West England of the influence of specialization on the management and outcome of patients with oesophageal and gastric cancers. Br J Surg 2002;89:914–22. 28. Dassen AE, Lemmens VE, van de Poll-Franse LV, et al. Trends in incidence, treatment and survival of gastric adenocarcinoma between 1990 and 2007: a population-based study in the Netherlands. Eur J Cancer 2010;46:1101–10. 29. Wouters MW, Wijnhoven BP, Karim-Kos HE, et al. High-volume versus low-volume for esophageal resections for cancer: the essential role of case-mix adjustments based on clinical data. Ann Surg Oncol 2008;15:80–7. 30. Louwman WJ, Aarts MJ, Houterman S, et al. A 50% higher prevalence of life-shortening chronic conditions among cancer
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patients with low socioeconomic status. Br J Cancer 2010;103:1742–8. Hannan EL, Radzyner M, Rubin D, Dougherty J, Brennan MF. The influence of hospital and surgeon volume on in-hospital mortality for colectomy, gastrectomy, and lung lobectomy in patients with cancer. Surgery 2002;131:6–15. Xirasagar S, Lien YC, Lin HC, et al. Procedure volume of gastric cancer resections versus 5-year survival. Eur J Surg Oncol 2008;34:23–9. Aiken LH, Clarke SP, Cheung RB, Sloane DM, Silber JH. Educational levels of hospital nurses and surgical patient mortality. JAMA 2003;290:1617–23. Songun I, Putter H, Kranenbarg EM, Sasako M, van de Velde CJ. Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial. Lancet Oncol 2010;11:439–49. Bonenkamp JJ, Songun I, Hermans J, et al. Randomised comparison of morbidity after D1 and D2 dissection for gastric cancer in 996 Dutch patients. Lancet 1995;345:745–8. Krijnen P, den Dulk M, Meershoek-Klein Kranenbarg E, JansenLandheer ML, van de Velde CJ. Improved survival after resectable
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non-cardia gastric cancer in The Netherlands: the importance of surgical training and quality control. Eur J Surg Oncol 2009;35:715–20. Leapfrog Group. Available from: http://www.leapfroggroup.org/. Jensen LS, Nielsen H, Mortensen PB, Pilegaard HK, Johnsen SP. Enforcing centralization for gastric cancer in Denmark. Eur J Surg Oncol 2010;36:S50–4. Birkmeyer JD, Sun Y, Goldfaden A, Birkmeyer NJO, Stukel TA. Volume and process of care in high-risk cancer surgery. Cancer 2006;106:2476–81. Wouters MW, Karim-Kos HE, le Cessie S, et al. Centralization of esophageal cancer surgery: does it improve clinical outcome? Ann Surg Oncol 2009;16:1789–98. Sonnenday CJ, Birkmeyer JD. A tale of two provinces: regionalization of pancreatic surgery in Ontario and Quebec. Ann Surg Oncol 2010;17:2535–6. Dikken JL, Lemmens VE, Wouters MWJM, et al. Increased incidence and survival for oesophageal cancer but not for gastric cardia cancer in the Netherlands. Eur J Cancer 2012, in press. http://dx.doi.org/10.1016/j.ejca.2012.01.009.
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Effect of hospital volume on postoperative mortality and survival after oesophageal and gastric cancer surgery in the Netherlands between 1989 and 2009 Johan L. Dikken a,b, Anneriet E. Dassen c, Valery E.P. Lemmens d, Hein Putter e, Pieta Krijnen f, Lydia van der Geest f, Koop Bosscha c, Marcel Verheij b, Cornelis J.H. van de Velde a,⇑, Michel W.J.M. Wouters a,g a
Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, The Netherlands Department of Radiotherapy, The Netherlands Cancer Institute – Antoni Leeuwenhoek Hospital, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands c Department of Surgery, Jeroen Bosch Ziekenhuis, Henri Dunantstraat 1, 5223 GZ Den Bosch, The Netherlands d Comprehensive Cancer Center South, Zernikestraat 29, 5612 HZ Eindhoven, The Netherlands e Department of Medical Statistics, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, The Netherlands f Comprehensive Cancer Center The Netherlands, Schuttersveld 2, 2316 ZA, Leiden, The Netherlands g Department of Surgery, The Netherlands Cancer Institute – Antoni Leeuwenhoek Hospital, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands b
KEYWORDS Oesophageal neoplasms Stomach neoplasms Gastrectomy Oesophagectomy Quality indicators – health care Quality assurance – health care Quality of health care Hospital mortality Survival
Abstract Background: High hospital volume is associated with better outcomes after oesophagectomy and gastrectomy. In the Netherlands, a minimal volume standard of 10 oesophagectomies per year was introduced in 2006. For gastrectomy, no minimal volume standard was set. Aims of this study were to describe changes in hospital volumes, mortality and survival and to explore if high hospital volume is associated with better outcomes after oesophagectomy and gastrectomy in the Netherlands. Methods: From 1989 to 2009, 24,246 patients underwent oesophagectomy (N = 10,025) or gastrectomy (N = 14,221) in the Netherlands. Annual hospital volumes were defined as very low (1–5), low (6–10), medium (11–20), and high (P21). Volume–outcome analyses were performed using Cox regression, adjusting for year of diagnosis, case-mix and the use of multimodality treatment. Results: From 1989 to 2009, the percentage of patients treated in high-volume hospitals increased for oesophagectomy (from 7% to 64%), but decreased for gastrectomy (from 8% to 5%). Six-month mortality (from 15% to 7%) and 3-year survival (from 41% to 52%) improved after oesophagectomy, and to a lesser extent after gastrectomy (6-month mortality:
⇑ Corresponding author: Address: Leiden University Medical Center, Department of Surgery, K6-R, P.O. Box 9600, 2300 RC Leiden, The Netherlands. Tel.: +31 71 526 2309; fax: +31 71 526 6750. E-mail address: [email protected] (C.J.H. van de Velde).
0959-8049/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ejca.2012.02.064
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15%-10%, three-year survival: 55–58%). High hospital volume was associated with lower 6month mortality (hazard ratio (HR) 0.48, P < 0.001) and longer 3-year survival (HR 0.77, P < 0.001) after oesophagectomy, but not after gastrectomy. Conclusions: Oesophagectomy was effectively centralised in the Netherlands, improving mortality and survival. Gastrectomies were mainly performed in low volumes, and outcomes after gastrectomy improved to a lesser extent, indicating an urgent need for improvement in quality of surgery and perioperative care for gastric cancer in the Netherlands. Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction Oesophageal and gastric cancers are highly lethal malignancies.1 Despite surgery, which is the cornerstone of curative treatment for these diseases, survival is low, and compared to other surgical procedures, postoperative mortality is high. In the Western world, 5-year survival rates are below 25% for oesophageal cancer,2,3 and do not exceed 40% for gastric cancer.2,4 Reported postoperative mortality after oesophagectomy varies from 2% for specialised centres5 to 10% for certain nationwide registries.6 After gastrectomy, postoperative mortality varies between 3% to well above 10%.7,8 To reduce mortality and improve survival, it has been suggested that these high-risk operations should be performed in specialised centres with adequate annual volumes. Many studies have investigated volume–outcome relations after oesophagectomy and gastrectomy, but the relative importance of volume after gastrectomy in particular is disputed.9,10 In the Netherlands, a relation between high hospital volume and low postoperative mortality was demonstrated for oesophagectomy in 2000.11 Despite extensive discussions within the Dutch Society of Surgery, this study did not lead to significant changes in referral patterns for oesophagectomies on a national level. Therefore, as of 2006 a minimum volume of 10 oesophagectomies per year was enforced by the Dutch Healthcare Inspectorate, and as of 2011 the Dutch Society of Surgery recommends a minimal volume of 20 oesophagectomies per year. For gastrectomy, no minimum volume standard has been established in the Netherlands. Aims of the present study were to describe changes in annual hospital volumes, postoperative mortality, survival and lymph node yields for oesophagectomy and gastrectomy in the Netherlands between 1989 and 2009, and to explore whether there is any association between annual hospital volume for oesophagectomy and gastrectomy and postoperative mortality, survival and lymph node yield.
Netherlands, a country of 16.5 million inhabitants. Information on all newly diagnosed malignancies is routinely collected by trained registrars from the hospital records 6–18 months after diagnosis. Quality and completeness of the data are high.12 Topography and morphology were coded according to the International Classification of Diseases for Oncology (ICD-O).13 ICD-O morphology codes were used to classify tumours as adenocarcinoma (8140-8145, 8190, 8201-8211, 8243, 8255-8401, 8453-8520, 8572, 8573, 8576), squamous cell carcinoma (SCC) (8032, 8033, 8051-8074, 8076-8123) and other or unknown histology (8000-8022, 8041-8046, 8075, 8147, 8153, 8200, 82308242, 8244-8249, 8430, 8530, 8560, 8570, 8574, 8575). Tumours were staged according to the International Union Against Cancer (UICC) Tumour Node Metastases (TNM) classification in use in the year of diagnosis. Vital status was initially obtained from municipal registries, and from 1994 onwards from the nationwide population registries network. These registries provide complete coverage of all deceased Dutch citizens. Follow-up was complete for all patients until 31st December 2009. The study was approved by the NCR Review Board. 2.2. Patients Between January 1989 and December 2009, 71,090 patients with oesophageal or gastric cancer were diagnosed in the Netherlands (Fig. 1). Patients who did not undergo surgical treatment (N = 43,646) and patients without information on the hospital where the diagnosis was established, or where surgery was performed (N = 8), were excluded, leaving 27,436 resections available to calculate annual hospital volumes. After establishing annual hospital volumes, patients with insitu carcinoma (N = 288), and patients with distant metastases (N = 2902) were excluded, leaving 24,246 patients with non-metastatic invasive carcinoma available for volume–outcome analyses. 2.3. Surgery
2. Patients and methods 2.1. The Netherlands Cancer Registry Data were obtained from the Netherlands Cancer Registry (NCR), which covers all hospitals in the
Since the NCR is a topography-based registry, and the type of surgery was not specified for every patient, the distinction between oesophageal and gastric cancer surgery was based on tumour location. Oesophagectomies were defined as resections for cancers of the
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J.L. Dikken et al. / European Journal of Cancer 48 (2012) 1004–1013 Netherlands Cancer Registry 1989-2009 Diagnosis of oesophageal orgastric cancer N = 71,090 Excluded (N = 43,646) No resection Excluded (N = 8) No hospital in registry Resection for oesophageal or gastric cancer N = 27,436
Calculation of Annual Hospital Volumes
Excluded (N = 3,190) In-situ/metastatic disease Resection for M0 oesophageal or gastric cancer N = 24,246
Mortality and Survival Analyses
Fig. 1. Study profile.
oesophagus (C15.0-15.9) and gastric cardia (C16.0), whereas gastrectomies were defined as resections for non-cardia gastric cancer (C16.1-16.9). To ensure this distinction did not influence the results, volume–outcome analyses were repeated with cardia cancer coded as gastric cancer. Yearly resection rates were calculated as the number of resections relative to the number of cancers diagnosed in a year. 2.4. Hospital volumes Annual hospital volumes were defined as the number of oesophagectomies or gastrectomies per hospital per year. Clinically relevant volume categories were defined as very low (1–5/year), low (6–10/year), medium (11–20/ year), and high (P21/year). From 2005 to 2009, the hospital where the surgery was performed was registered for all patients. Before 2005, the hospital where the surgery was performed was only registered in 53% of the cases, and showed an 80% overlap with the hospital of diagnosis. For the remaining 47%, with an unknown surgical hospital, the hospital of diagnosis was used to calculate hospital volume. 2.5. Statistical analysis Oesophagectomy and gastrectomy were analysed separately. Resection rates and hospital volumes over time were analysed with the Chi-square test. Changes in 6month mortality and 3-year survival were analysed with stratified Cox regression, adjusted for sex, age, socioeconomic status,14 stage, morphology, preoperative therapy use and postoperative therapy use (only for 3year survival). Overall survival (OS) was calculated from the day of diagnosis until death, because the date of surgery was not available before 2005. Six-month OS was calculated unconditionally, while 3-year OS was calculated conditionally on surviving the first 6 months after
diagnosis. Lymph node yields over time were adjusted for sex, age, stage and morphology. For volume–outcome analyses, the patient was considered the unit of analysis, with hospital volume as the exposure factor. Differences in survival estimates were calculated with Cox regression, stratified for hospital volume and adjusted for the factors used to analyse changes over time and for clustering of deaths within hospitals.15 Differences in lymph node yields were analysed with generalised estimated equations, adjusted for the factors used to analyse changes over time and for clustering within hospitals. Besides analysing hospital volume in categories, annual volume was analysed as a linear variable. Analyses were performed with SPSS (version 17.0.2) and R (version 2.12.2). 3. Results 3.1. Patient characteristics Between 1989 and 2009, 24,246 patients with resectable, non-metastatic oesophageal (N = 10,025) or gastric cancer (N = 14,221) underwent a resection in the Netherlands. Patient characteristics (Tables 1 and 2) varied between the different volume categories. For oesophageal cancer, high-volume hospitals treated more patients with squamous cell carcinoma and more advanced tumour stages. For gastric cancer, patients treated in high-volume hospitals were older and had more advanced tumours. 3.2. Hospital volumes over time From 1989 to 2009, the annual number of oesophagectomies doubled (from 352 to 723), and the annual number of gastrectomies steadily decreased (from 1107 to 495) (Fig. 2).
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Table 1 Patient characteristics for all surgically treated patients with non-metastatic invasive oesophageal cancer in the Netherlands between 1989 and 2009 (N = 10,025). VLV (1–5)
Total Sex Male Female Age category <60 60–75 >75 SES Low Medium High Unknown Morphology Adenocarcinoma SCC Other TNM stage I II III IVa Unknown Preoperative therapy Yes No Postoperative therapy Yes No
LV (6–10)
MV (11–20)
HV (P21)
P
N
%
N
%
N
%
N
%
2914
100
2695
100
1494
100
2922
100
2213 701
76 24
2058 637
76 24
1130 364
76 24
2249 673
77 23
0.73
936 1630 348
32 56 12
956 1456 283
35 54 11
515 814 165
34 54 11
1032 1632 258
35 56 9
0.002
274 2415 135 90
9 83 5 3
308 2124 123 140
11 79 5 5
165 1208 53 68
11 81 4 5
259 2131 115 417
9 73 4 14
<0.001
2288 554 72
79 19 2
2006 628 61
74 23 2
1113 341 40
74 23 3
2134 732 56
73 25 2
<0.001
622 1161 988 30 113
21 40 34 1 4
512 1093 940 30 120
19 41 35 1 4
285 576 535 23 75
19 39 36 2 5
522 1068 1112 25 195
18 37 38 1 7
<0.001
165 2749
6 94
244 2451
9 91
357 1137
24 76
938 1984
32 68
<0.001
144 2770
5 95
145 2550
5 95
91 1403
6 94
151 2771
5 95
0.43
VLV: Very Low Volume (1–5 resections/year) LV: Low Volume (6–10 resections/year), MV: Medium Volume (11–20 resections/year), HV: High Volume (P21 resections/year), SES: Socio Economic Status, SCC: squamous cell carcinoma, preoperative/postoperative therapy: chemotherapy with/without radiotherapy. a T4N1-3M0 and T1-4N3M0 gastric cancers were assigned stage IV in the 6th edition TNM-classification
The percentage of oesophagectomies performed in high-volume hospitals increased from 7% to 64%, while the number of gastrectomies performed in high-volume hospitals decreased from 8% to 5%. In 2009, 44 of the 92 hospitals (48%) in the Netherlands performed oesophagectomies, and 91 of the 92 hospitals performed gastrectomies. 3.3. Resection rates, mortality, survival and lymph node yields over the years Resection rates slightly decreased for oesophageal cancer (from 1989 to 2009: 31–29%, P < 0.01), and strongly decreased for gastric cancer (56–37%, P < 0.01). Adjusted 6-month mortality after oesophagectomy decreased from 14.8% in 1989 to 7.1% in 2009 (P < 0.001), while adjusted 6-month mortality after gastrectomy decreased to a lesser extent: from 15.2% in 1989 to 9.9% in 2009 (P < 0.001) (Fig. 3a). Adjusted 3year conditional survival significantly increased after oesophagectomy: from 41.0% in 1989 to 52.2% in 2009 (P < 0.001). Adjusted 3-year conditional survival after
gastrectomy increased to a lesser extent: from 55.0% in 1989 to 58.4% in 2009 (P < 0.01) (Fig. 3b). The improvement in 6-month mortality and 3-year survival over time was significantly stronger after oesophagectomy, when compared to gastrectomy (both P < 0.01). Mean lymph node yield after oesophagectomy increased from 10.1 in 1999 to 16.2 in 2009 (P < 0.001), and mean lymph node yield after gastrectomy increased from 8.1 in 1999 to 12.4 in 2009 (P < 0.001). 3.4. Volume–outcome relations Results from the multivariable analyses on volume– outcome relations are shown in Table 3. After oesophagectomy, medium and high volume hospitals were associated with lower six-month mortality and longer three-year conditional survival when compared to very-low volume hospitals (Fig. 4). After gastrectomy, neither six-month mortality or three-year conditional survival were associated with hospital volume category (Fig. 5). High hospital volume was associated with high
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Table 2 Patient characteristics for all surgically treated patients with non-metastatic invasive gastric cancer in the Netherlands between 1989 and 2009 (N = 14,221). VLV (1-5)
Total Sex Male Female Age category <60 60–75 >75 SES Low Medium High Unknown Morphology Adenocarcinoma Other TNM stage I II III IVa Unknown Preoperative therapy Yes No Postoperative therapy Yes No
LV (6-10)
MV (11-20)
HV (P21)
P
N
%
N
%
N
%
N
%
3411
100
6099
100
4356
100
355
100
1987 1424
58 42
3707 2392
61 39
2646 1710
61 39
224 131
63 37
0.045
689 1606 1116
20 47 33
1270 2917 1912
21 48 31
837 2074 1445
19 48 33
53 165 137
15 46 39
0.016
378 2665 118 250
11 78 3 7
783 4846 230 240
13 79 4 4
560 3559 106 131
13 82 2 3
53 294 8 0
15 83 2 0
<0.001
3336 75
98 2
5985 114
98 2
4287 69
98 2
352 3
99 1
0.11
1299 898 936 181 97
38 26 27 5 3
2279 1675 1718 248 179
37 27 28 4 3
1687 1187 1204 154 124
39 27 28 4 3
147 78 111 11 8
41 22 31 3 2
0.014
167 3244
5 95
303 5796
5 95
138 4218
3 97
8 347
2 98
<0.001
139 3272
4 96
236 5863
4 96
122 4234
3 97
12 343
3 97
0.009
VLV: Very Low Volume (1–5 resections/year) LV: Low Volume (6–10 resections/year), MV: Medium Volume (11–20 resections/year), HV: High Volume (P21 resections/year), SES: Socio Economic Status, preoperative/postoperative therapy: chemotherapy with/without radiotherapy. a T4N1-3M0 and T1-4N3M0 gastric cancers were assigned stage IV in the 6th edition TNM-classification
lymph node yield both after oesophagectomy and gastrectomy. When analysing hospital volume as a linear covariate, volume–survival results remained the same. No changes in the results were found when volume–outcome relations were analysed with surgery for cardia cancer coded as gastrectomy (data not shown). 4. Discussion Over the study period, the number of oesophagectomies performed in high volume hospitals considerably increased, while in 2009 most gastrectomies were performed in low volume hospitals. Both 6-month mortality and 3-year survival improved after oesophagectomy, but to a lesser extent after gastrectomy. In the current dataset, a volume–survival relation was revealed for oesophagectomy, but not for gastrectomy. Since Luft et al. published the first study on volume– outcome relations for surgery,16 many studies have emerged investigating the effect of hospital and surgeons volume on short term and long term outcomes for a
variety of diseases, including resections for oesophageal and gastric cancers. Several large studies have shown an association between high hospital volume and low postoperative mortality both for oesophagectomy, 17–20 and gastrectomy17,20–22, but other studies did not find an association.23–25 In a meta-analysis exploring volume– outcome relations, high volume surgery was associated with lower postoperative mortality after both oesophagectomy and gastrectomy.9 A limited number of studies investigate the relation between hospital volume and long-term survival after oesophagectomy and gastrectomy, with conflicting results.7,24,26,27 Over the past two decades, the number of oesophagectomies in the Netherlands has increased, corresponding with an increasing incidence of oesophageal cancer.42 The decreasing incidence of gastric cancer explains the low number of gastrectomies currently performed in the Netherlands.28 Furthermore, the resection rate for gastric cancer dropped significantly, most likely the result of improved preoperative staging. Combined with the almost complete disappearance of surgery for reflux disease and ulcers, surgeons are decreasingly exposed to gastrectomies. This might partly be compensated by
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a 20 ≥21 11-20 6-10 1-5
6-Month Mortality (%)
Number of Resections
a
600
400
200
0 1989
1993
1997
2001
2005
10
5
0
2009
1989
1993
1997
2001
2005
2009
Year of Diagnosis
1,200
≥21 11-20 6-10 1-5
1,000
b 60 50
3-Year Survival (%)
Number of Resections
Oesophagectomy Gastrectomy
15
Year of Diagnosis
b
1009
800 600 400
Oesophagectomy Gastrectomy
40 30 20
200 10 0 1989
1993
1997
2001
2005
2009
0
Year of Diagnosis
1989
1993
1997
2001
2005
Year of Diagnosis
increasing volumes of bariatric surgery for obesity, but the surgical techniques used differ significantly. In the current study, increasing hospital volume was associated with lower mortality and increased long-term survival after oesophagectomy, but not after gastrectomy. This observation for gastrectomies might be explained by the low number of high-volume gastrectomies (2.5% of all gastrectomies in the current dataset), and the low threshold for what was considered high-volume surgery. In other studies that did find an association between gastrectomy in high volumes and good outcomes, the lower limit of high volume surgery varied from 20/year up to 264/year.17,27 The current study covers an extensive period of two decades of oesophago-gastric cancer surgery in the Netherlands, and analyses a significant population of about 25,000 patients. Unlike many of the large volume–outcome studies, the current study uses a clinical database with highly reliable data, providing complete coverage of all diagnosed cancers in the Netherlands. Furthermore, outcomes are case-mix adjusted, increasing reliability of the results.29 The absence of comorbidity in the current dataset was partly compensated by the use of SES, which can be considered a proxy for comorbidity.30 A potential bias when analysing outcomes over a long period is that preoperative staging and (perioperative)
c Mean Lymph Node Yield
Fig. 2. (a) Number of oesophagectomies per hospital volume category. (b) Number of gastrectomies per hospital volume category.
20
15
10
5 Oesophagectomy Gastrectomy
0 1999
2001
2003
2005
2007
2009
Year of Diagnosis
Fig. 3. (a) Six-month mortality for oesophagectomy and gastrectomy, adjusted for sex, age, socio-economic status, stage, morphology and use of preoperative therapy (1989–2009). Oesophagectomy, hazard ratio (HR) 0.96 for each year, P < 0.001. Gastrectomy, HR 0.98 for each year, P < 0.001. Difference between oesophagectomy and gastrectomy: P = 0.003. (b) Three-year survival rate conditional on surviving the first 6 months for oesophagectomy and gastrectomy, adjusted for sex, age, socio-economic status, stage, morphology and use of preoperative and postoperative therapy (1989–2006). Oesophagectomy, HR 0.97 for each year, P < 0.001. Gastrectomy, HR 0.99 for each year, P < 0.001. Difference between oesophagectomy and gastrectomy: P < 0.001. (c) Median lymph node yield for oesophagectomy and gastrectomy, adjusted for sex, age, stage and morphology (1999–2009). Oesophagectomy: P < 0.001. Gastrectomy: P < 0.001.
care generally improve over time. For example, endoscopic ultrasound, multislice high resolution
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Table 3 Volume–outcome relations for oesophagectomy and gastrectomy (1989–2009). Mortality and survival were calculated with multivariable Cox regression, nodal yield was calculated with generalised estimated equations. Oesophagectomy
Gastrectomy a
Hospital volume Very low (1–5/yr) Low (6–10/yr) Medium (11–20/yr) High (P21/yr) Year of diagnosis 1989–1993 1994–1997 1998–2001 2002–2005 2006–2009 Sex Male Female Age category <60 60–75 >75 SES Low Medium High Unknown TNM stage I II III IV Unknown Morphology Adenocarcinoma SCC Other Preoperative therapy No Yes Postoperative therapy No Yes
b
Six-month mortality Three-year survival
LN yield
Six-month mortality Three-year survivala LN yieldb
HR
95% CI
HR
95% CI
OR 95% CI
HR
1.00 0.90 0.78 0.48
0.78–1.03 0.62–0.97 0.38–0.61
1.00 1.01 0.90 0.77
0.94–1.10 0.81–0.99 0.70–0.85
1.00 0.91 0.82 0.69 0.67
0.78–1.07 0.68–0.98 0.55–0.86 0.52–0.85
1.00 0.92 0.88 0.69 0.75
1.00 0.75
0.66–0.86
1.00 1.83 3.10
95% CI
HR
95% CI
OR 95% CI
1.00 1.00 1.00 0.91–1.09 0.95 1.10 1.00–1.22 0. 95 1.50 1.25–1.80 1. 10
0.84–1.07 0.83–1.08 0.82–1.49
1.00 0.99 0.99 0.98
0.91–1.07 0.90–1.08 0.86–1.12
1.00 1.02 0.96–1.08 0.99 0.90–1.10 1.93 1.81–2.04
0.83–1.01 0.79–0.97 0.63–0.75 0.63–0.75
1.00 0.96 1.00 0.89 1.18 1.10–1.25 0.74 1.42 1.27–1.60 0.70
0.86–1.07 0.79–1.01 0.65–0.85 0.60–0.81
1.00 0.98 0.94 0.88 0.78
0.90–1.05 0.87–1.02 0.81–0.96 0.72–0.86
1.00 1.08 1.02–1.16 1.42 1.32–1.52
1.00 0.83
0.78–0.89
1.00 1.00 1.04 1.00–1.08 0.79
0.73–0.85
1.00 0.91
0.85–0.97
1.10 1.05–1.14
1.56–2.14 2.54–3.79
1.00 1.14 1.41
1.07–1.21 1.25–1.59
1.00 1.00 0.97 0.94–1.00 2.03 0.87 0.82–0.92 3.94
1.78–2.30 3.47–4.49
1.00 1.27 1.57
1.18–1.37 1.44–1.71
1.00 0.88 0.82–0.93 0.75 0.69–0.81
1.00 0.76 0.54 0.53
0.64–0.90 0.38–0.78 0.38–0.74
1.00 1.05 1.00 1.04
0.96–1.16 0.85–1.17 0.86–1.26
1.00 0.92 0.70 0.94
0.81–1.04 0.55–0.91 0.73–1.21
1.00 1.01 1.00 1.03
0.92–1.12 0.84–1.20 0.85–1.24
1.00 1.28 1.73 3.85 1.92
1.08–1.52 1.41–2.13 2.55–5.81 1.41–2.62
1.00 2.74 5.20 9.76 2.37
2.46–3.04 4.46–6.05 7.43–12.81 2.00–2.81
1.00 1.15 1.39 1.93 1.04
1.00 1.46 2.15 3.50 1.91
1.31–1.63 1.93–2.38 3.00–4.08 1.40–2.60
1.00 2.99 5.37 8.45 2.36
2.78–3.22 5.01–5.75 7.43–9.61 1.96–2.84
1.00 1.26 1.28
1.11–1.43 0.94–1.75
1.00 1.09 1.05
0.98–1.21 0.84–1.33
1.00 1.00 1.05 0.99–1.11 1.00 0.88–1.12 1.18
0.86–1.64
0.58
0.44–0.78
1.00 0.32
0.23–0.43
1.00 0.84
0.76–0.93
1.00 0.27
0.17–0.43
1.00 1.05
0.84–1.31
1.00 1.07
0.94–1.21
1.00 1.01
0.85–1.21
1.00
1.09–1.21 1.31–1.47 1.70–2.20 0.92–1.17
1.00 1.23 1.55 2.23 1.01
1.16–1.31 1.46–1.66 2.05–2.42 0.82–1.24
1.00 0.94 0.71–1.25
HR: hazard ratio, OR: odds ratio, SES: Socio Economic Status, SCC: squamous cell carcinoma, CI: confidence interval, Bold: significant (P < 0.05). a Conditional on surviving the first six months. b 1999–2009.
computed tomography and PET computed tomography were introduced resulting in improvement of staging. Hospital volumes for oesophagectomy significantly change during the study period, with most high-volume resections performed in the more recent years. Therefore, high volume resections are intrinsically associated with better outcomes. However, adjusting for year of diagnosis offsets this effect. Another potential weakness is the unavailability of the surgery hospital for part of the patients treated before 2005. Instead, the hospital of diagnosis was used. However, this only happened in the first years of the study, when hospitals less frequently referred patients to another hospital for surgery.
A point of discussion might be that volumes are analysed on hospital level, rather than surgeon level.27,31,32 Quality of care, however, consists of more than an individual surgeon’s performance. Perioperative care, anaesthesia, ICU staffing, experience of the nursery staff and collaboration between different disciplines all contribute to outcomes associated with the performed procedure.33 The role of the surgeon is only one, yet important, factor contributing to outcome. Initiatives to improve medical and especially surgical care are legion. Randomised trials improve care by selecting appropriate treatments for certain indications,3,34 and by educating surgeons participating in
J.L. Dikken et al. / European Journal of Cancer 48 (2012) 1004–1013
a
20
High Volume* Medium Volume* Low Volume Very Low Volume
(≥21/yr) (11−20/yr) (6−10/yr) (0−5/yr)
a
* P < 0.05
High Volume Medium Volume Low Volume Very Low Volume
(≥21/yr) (11−20/yr) (6−10/yr) (0−5/yr)
15
Mortality (%)
15
Mortality (%)
20
10
10
5
5
0
0 0
1
2
3
4
5
0
6
1
2
* P < 0.05
b Overall survival (%)
Overall survival (%)
100
80
60
40
High Volume* Medium Volume* Low Volume Very Low Volume
20
(≥21/yr) (11−20/yr) (6−10/yr) (0−5/yr)
0 0
6
12
18
24
30
36
Time (Months)
3
4
5
6
Time (Months)
Time (Months)
b
1011
100
80
60
40 High Volume Medium Volume Low Volume Very Low Volume
20
(≥21/yr) (11−20/yr) (6−10/yr) (0−5/yr)
0 0
6
12
18
24
30
36
Time (Months)
Fig. 4. Volume–outcome relations for oesophagectomy. (a) Relation between volume and 6-month survival, adjusted for year of diagnosis, sex, age, socio-economic status, stage, morphology and preoperative therapy use. *P < 0.05 compared to Very Low Volume. (b) Relation between volume and 3-year survival, conditional on surviving the first 6 months, adjusted for year of diagnosis, sex, age, socio-economic status, stage, morphology and preoperative and postoperative therapy use. *P < 0.05 compared to Very Low Volume.
Fig. 5. Volume–outcome relations for gastrectomy. (a) Relation between volume and 6-month survival, adjusted for year of diagnosis, sex, age, socio-economic status, stage, morphology and preoperative therapy use. *P < 0.05 compared to Very Low Volume. (b) Relation between volume and 3-year survival, conditional on surviving the first 6 months, adjusted for year of diagnosis, sex, age, socio-economic status, stage, morphology and preoperative and postoperative therapy use. *P < 0.05 compared to Very Low Volume.
the trial.35,36 However, the majority of cancer patients are treated outside trials, and especially improvements in the process and structure of care on a nation-wide level will bring benefit to this group of patients. Many studies have advocated the centralisation of low-volume, high-risk operations, thereby improving nationwide quality of care.11,27 Centralisation of oesophageal and gastric cancer is currently performed in several European countries, whereas referral to high-volume centres is also advocated in the United States by the Leapfrog group.37 In Denmark, centralisation of gastric cancer surgery from 37 to 5 hospitals leaded to a drop in postoperative mortality from 8.4% to 2.1% over a period of 5 years.38 Unlike the Netherlands, which is a relatively small country with good infrastructure, centralisation of care in countries with large rural areas might lead to unreasonable travel burdens and problems with continuity of care after surgery. Therefore, others have advocated implementing processes that are related to excellent outcomes in low volume hospitals, but identification of these processes remains challenging.39
Meanwhile, using hospital volume as the sole basis for referral to improve outcomes is criticised.17 Although hospital volume can reliably identify groups of hospitals with better results on average, individual low volume hospitals can have excellent outcomes and vice versa. In contrast to volume-based referral, outcome based-referral avoids this problem, and has proven its value for oesophagectomy in the Western part of the Netherlands. In this area, a prospective audit was conducted to identify hospitals with excellent performance in oesophagectomy. During the five-year audit, a gradual concentration towards centres with excellent performance occurred, leading to a drop in postoperative mortality (12–4%) and an improvement in survival.40 Combining centralisation with auditing substantially adds to improvement of care.41 With auditing, providers of care are monitored and their performance is benchmarked against their peers. Auditing is performed on a national level for oesophagogastric cancer in Denmark,38 Sweden and the United Kingdom. A nationwide audit for both oesophageal and gastric cancer surgeries has started in the Netherlands as of 2011 aiming for
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complete coverage of all oesophagectomies and gastrectomies. In conclusion, enforcing centralisation for oesophagectomy in the Netherlands has resulted in a shift in annual hospital volumes: most resections are currently performed in high volume centres. For gastrectomy, no minimum number of resections was required, and the majority of gastric cancer resections were performed in low volume hospitals. However, as of 2012 gastrectomies in the Netherlands will be centralised to a minimum of 10/year, and as of 2013 to a minimum of 20/year. Oesophagectomy in high volume hospitals is associated with improved outcomes. No such relation for gastric cancer could be established in the current dataset, but only a minority of patients was treated in high volume hospitals. Over the past two decades, short-term mortality and longterm survival after oesophagectomy decreased significantly, while outcomes after gastrectomy improved to a lesser extent, indicating an urgent need for improvement in quality of surgery and perioperative care for gastric cancer in the Netherlands. Role of funding source This study was funded by the Signalling Committee on Cancer of the Dutch Cancer Society (KWF Kankerbestrijding). This funding source had no role in study design, collection, analysis, interpretation, writing of the manuscript or in the decision to submit the manuscript for publication. Conflict of interest statement None declared. References 1. Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127:2893–917. 2. SEER Cancer Statistics Review, 1975–2007. National Cancer Institute. Bethesda, MD, 2011. Available from: http://seer.cancer.gov/csr/1975_2007/. 3. Hulscher JB, Tijssen JG, Obertop H, van Lanschot JJ. Transthoracic versus transhiatal resection for carcinoma of the esophagus: a meta-analysis. Ann Thorac Surg 2001;72:306–13. 4. Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 2006;355:11–20. 5. Siewert JR, Stein HJ, Feith M, et al. Histologic tumor type is an independent prognostic parameter in esophageal cancer: lessons from more than 1000 consecutive resections at a single center in the Western world. Ann Surg 2001;234:360–7 [discussion 8–9]. 6. Bailey SH, Bull DA, Harpole DH, et al. Outcomes after esophagectomy: a ten-year prospective cohort. Ann Thorac Surg 2003;75:217–22 [discussion 22]. 7. Hannan E. The influence of hospital and surgeon volume on inhospital mortality for colectomy, gastrectomy, and lung lobectomy in patients with cancer. Surgery 2002;131:6–15.
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